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W Lichtenegger

Publications and source records attributed to W Lichtenegger.

At least 19 recordsLinked to original sources

p21 (WAF1/CIP1) protein expression is associated with prolonged survival but not with p53 expression in epithelial ovarian carcinoma.

OBJECTIVE: The objective of this study was to clarify the influence of p21 protein expression in ovarian cancer. p21 (WAF1 [wild-type p53 activated fragment 1]/CIP1) is a universal cyclin-dependent kinase inhibitor and can be induced as a downstream effector of the p53 tumor suppressor gene. METHODS: The expression of p21 was evaluated by immunohistochemical analysis with the monoclonal antibody WAF1 (Oncogene Science) on 106 formalin-fixed, paraffin-embedded tissue samples of epithelial ovarian cancer. RESULTS: p21 was expressed in 65 (61%) of all cases. p21 expression was associated with early stage in FIGO classification (FIGO I and II, P = 0.003) and no tumor residues after primary tumor resection (P = 0.018). Immunohistochemical staining results were judged as negative if no tumor nuclei were stained, as weak positive if 1-49% were stained, and as strong positive if over 50% of nuclei were stained. Clinical follow-up showed a better overall survival for cases with strong p21 expression (79 months) versus 40 months for weak expression and 30 months for no expression (P = 0.033). Previously determined p53 expression of this cohort was compared with p21 status. p53 overexpression was observed in 49 cases (48%) and showed no association with p21 expression. CONCLUSION: No correlation was found between p21 and p53 expression. p21 expression is a significant prognostic marker for improved survival in ovarian cancer and is associated with early FIGO stage and zero tumor residues after primary tumor resection.

Adult↗

Nitroglycerin application during cesarean delivery: plasma levels, fetal/maternal ratio of nitroglycerin, and effects in newborns.

OBJECTIVE: We sought to investigate maternal and fetal nitroglycerin metabolization and to assess the clinical condition of neonates after intravenous nitroglycerin application during cesarean delivery. STUDY DESIGN: At the time of the uterine puncture incision, either 0. 25 mg or 0.5 mg nitroglycerin or a physiologic sodium chloride solution was administered as an intravenous bolus. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and in umbilical blood samples taken immediately after cord clamping. Arterial blood pressure, pulse rates, and Apgar scores were recorded for the neonates 1, 5, and 10 minutes after birth. RESULTS: Sixty-two patients were included in the pharmacokinetic study. Median maternal plasma levels 1 and 5 minutes after injection of 0.5 mg nitroglycerin were 80 and 3.2 ng/mL, respectively; median maternal plasma levels 1 and 5 minutes after injection of 0.25 mg nitroglycerin were 38 and 1.2 ng/mL, respectively. In the umbilical vein 1 minute after application of 0. 5 mg or 0.25 mg nitroglycerin, the plasma levels were 0.41 and 0.09 ng/mL, respectively, and in the umbilical artery they were 0.03 and 0.008 ng/mL, respectively. Circulatory parameters and Apgar scores in the neonates did not differ significantly from those found in the placebo group. CONCLUSION: The level of nitroglycerin in umbilical plasma was two to three orders of magnitude lower than that found in maternal plasma and clearly in a subtherapeutic range. There was no indication that prenatal application of nitroglycerin to facilitate obstetric management is hazardous for neonates.

Adolescent↗

Comparison of the relaxation effect in vitro of nitroglycerin vs. fenoterol on human myometrial strips.

AIMS: Substance dose-related comparison of relaxation effect of nitroglycerin (GTN) and the beta 2-mimetic substance fenoterol in human myometrial tissue. METHODS: Test criterion is the isometric force development of isolated human myometrial strips. These muscle strips were removed from the lower uterine segment at cesarean section. Fenoterol in concentrations of 3 x 10(-8)-10(-5) mol/l or GTN in concentrations of 1.7 x 10(-8)-5.8 x 10(-4) mol/l were applied to the 2 x 2 x 10-mm strips, which were fixed and maintained in tissue baths. The curves were plotted on line. The integral or the "area under the curve" (AUC) served as the parameter for muscle strip activity. RESULTS: A total of 100 strips from 20 patients were used. GTN demonstrated a significant relaxation effect in the in vitro model on human myometrial strips from pregnant women already treated with oxytocin. The effect was able to be enhanced to a point where oxytocin-induced contractions were completely absent. A relatively clear connection was demonstrated between dose and effect whereby increased muscle relaxation resulted at increased concentrations. Compared to GTN application, muscle strip relaxation was less pronounced under fenoterol; a complete inhibition of myometrial activity was not achieved under fenoterol. CONCLUSIONS: With respect to relaxation of the myometrial tissue samples the NO donor GTN is at least as potent as the standard tocolytic agent fenoterol in the in vitro model.

Adrenergic beta-Agonists↗

Pre-operative staging of cervical cancer: comparison of magnetic resonance imaging (MRI) and computed tomography (CT) with histologic results.

Thirty-two patients with histologically confirmed cervical carcinoma were preoperatively investigated using MRI; in addition, a CAT-scan was performed on 15 of these patients. The diagnostic results using both modalities were compared with the histological findings (after hysterectomy according to Wertheim-Meigs, including lymph node dissection in the pelvic and, in part, in para-aortal regions). Determination of tumour volume was possible with high accuracy using MRI. Accuracy in assessing the parametria was 86%, vagina 90%, bladder and rectum 97%. The shortcoming of MRI is still the detection of infiltrated lymph nodes. The accuracy of 69% achieved for lymph nodes is equal to results with computed tomography. The general accuracy for our patients in staging was 81% for MRI versus 47% for CT. MRI-based diagnosis enables us to determine a correct tumour staging preoperatively, and is therefore very helpful in planning an adequate therapy. If MRI were used more widely it would contribute to simplification and shortening of the preoperative diagnostic procedure in patients with cervical carcinoma.

Adult↗

[Dose intensified adjuvant chemotherapy in high risk breast carcinoma with 4-9 positive lymph nodes].

OBJECTIVE: Taxanes and anthracyclines represent the two most active groups of agents for the treatment of breast cancer. We evaluated this combination in patients with more than 3 positive lymph nodes in an adjuvant, dose-intensive, sequential therapy in comparison with the standard chemotherapy regimen epirubicin/cyclophosphamide in relation to toxicities. MATERIAL AND METHODS: Since 9/96 127 patients with 4-9/over 9 positive lymph nodes have been recruited from 21 participating centers in an ongoing trial. 67 patients were prospectively randomised for first-line chemotherapy to treatment group A (epirubicin 90 mg/m2-paclitaxel 175 mg/m2; 4 cycles bi-weekly, supported by G-CSF 5 micrograms/kg day 5-13 and 3 sequential cycles of CMF 600/40/600 mg/m2 at 2-weeks interval) and 60 patients to treatment group B (epirubicin 90 mg/m2-cyclophosphamide 600 mg/m2, 4 cycles tri-weekly, and 3 sequential cycles of CMF 600/40/600 mg/m2 at 3-weeks interval). RESULTS: Preliminary safety and toxicity data are evaluable for 679 cycles. Data about response rate and disease-free-survival and overall survival will be delivered later. For the hematological toxicity the main grade 3 and 4 adverse events for A vs. B were: leucopenia 9.8% vs. 8.4%, febrile neutropenia 1.6% vs. 0.8%--anemia (< 5.9 mmol/l), 0.4% vs. 0.2%--thrombopenia 0% vs. 0%. Non-hematological toxicity occurred more frequently in group A (grade 2, 3, 4):--neuropathy 4.4% vs. 0%,--nausea/emesis 27.8% vs. 19.3%,--fatigue 14.6% vs. 3.4% and mucositis 2.8% vs. 0.3%.

Antineoplastic Combined Chemotherapy Protocols↗

Comparison of various imaging methods with particular evaluation of color Doppler sonography for planning surgery for breast tumors.

OBJECTIVE: Color Doppler sonography (CD) was compared with other diagnostic imaging methods [mammography (MG), breast ultrasound (US) and magnetic resonance imaging (MRI)] in the planning of surgery for breast tumors. MATERIALS AND METHODS: 99 patients with breast cancer and 101 with ultimately benign breast lesions were examined preoperatively. The specificity and sensitivity were calculated, as well as the predictive values. Various qualitative and semiquantitative CD parameters were also analysed for their diagnostic value. RESULTS: The sensitivity/specificity of the various methods (in %) was: MG 85/77; US 95/80; CD 82/75; MRI 90/63. The positive predictive value (ppv)/negative predictive value (npv) (in %) was: MG 79/83; US 81/94; CD 72/84; MRI 79/63. The median maximum systolic flow velocity and the resistance index (RI) were significantly higher in breast cancer vessels than in benign lesions. The number of pulsating color pixels detected by CD was significantly higher for breast cancer. In cases of breast cancer significantly more blood flows were detected in the body of the tumor than at its periphery. CONCLUSION: Color Doppler sonography was not superior to other diagnostic methods for preoperative assessment of a breast lesion. The combination of all diagnostic procedures gave a correct classification rate of 93.3% and is much better than the correct classification of any single diagnostic imaging procedure.

Aged↗

Dose- intensified, preoperative and adjuvant chemotherapy in patients with T3- and T4- breast cancer: toxicity, clinical and pathological remission.

OBJECTIVE: The aim of the study was to investigate a dose-intensified, preoperative chemotherapy with 3 cycles (cy) of epirubicin 60 mg/m2, ifosfamide 5 g/m2 with mesna 5 g/m2, biweekly with G-CSF 5 micrograms/kg (filgrastim), in terms of toxicity, clinical and pathological remission rates and changes of immunohistochemical characteristics (ER, PR, c-erbB2, p53) during chemotherapy of inoperable patients (pt) with poor prognosis (locally advanced (LABC, 9 pt), inflammatory breast cancer (IBC, 12 pt) and M0. PATIENTS AND METHODS: Following preoperative chemotherapy (63 cy) and mastectomy patients received adjuvant 3 cy of epirubicin 60 mg/m2 and paclitaxel 175 mg/m2 (biweekly) with G-CSF (54 cy), and subsequently radiation of the thoracic wall and tamoxifen 20 mg/day. RESULTS: Primary toxicity (T): grade 3 alopecia (21 pt), grade 3-4 leucopenia (7 cy), grade 1-2 leucopenia (26 cy), grade 1-2 anemia (61 cy), grade 1-2 neurocortical T (13 cy), grade 1-2 neurosensory T (7 cy), grade 1 cardiac toxicity (1 pt). ORR: 65% (CR: 0 pt, PR: 13 pt, NC: 8 pt). The grades of histological regression were: 0: 14 pt, 1: 6 pt, 2: 0 pt, 3: 1 pt. No significant correlation was observed between the clinical response and the histological regression (Fischer's exact test). The immunohistochemical expression of tumor characteristics did not change significantly during preoperative chemotherapy (Wilcoxon test). 81% of the pt were disease-free after a median follow-up of 20 months (7-26). CONCLUSION: This therapy is safe, feasible and effective, both as primary and adjuvant chemotherapy in women with LABC and IBC.

Adult↗

Prognostic significance of DNA content and S-phase fraction in epithelial ovarian carcinomas analyzed by image cytometry.

The objective of this study was to evaluate the prognostic significance of DNA ploidy and S-phase fraction (SPF) in epithelial ovarian carcinomas analyzed by image cytometry. Frozen tissue of 103 epithelial ovarian carcinomas was analyzed for DNA ploidy and SPF with a Cell Analysis System Image Analyser (CAS 200, Becton-Dickinson) and correlations with clinical and histomorphologic factors and time to progression and overall survival were evaluated by univariate and multivariable analysis. Fifty-four percent of the ovarian carcinomas were found to be diploid, 38% aneuploid, and 8% tetraploid. The S-phase fraction was low (<5%) in 27%, intermediate (5-14.5%) in 47%, and high (>/=14.5%) in 26% of the patients. By univariate analysis overall survival and time to progression were significantly correlated with the S-phase fraction (P = 0.003 and P = 0.003), but not with DNA ploidy (P = 0. 31 and P = 0.51). A DNA index > 1.4 was correlated with poor outcome but the result did not achieve formal statistical significance (P = 0.08 and P = 0.12). A high SPF was a strong predictor of early recurrence, while a low SPF identified patients with a favorable long-term outcome. Other significant predictors of survival were FIGO stage, grade of differentiation, presence of distant metastasis, residual tumor, lymph node metastasis, and patient age. In multivariable statistical analysis only FIGO stage, histologic grade, and residual tumor after surgery were independent predictors of overall survival and time to progression.

Adult↗

Nitroglycerin to facilitate fetal extraction during cesarean delivery.

OBJECTIVE: To determine the efficacy of nitroglycerin in easing fetal extraction in elective cesarean deliveries in comparison with placebo and to collect maternal and fetal pharmacologic data after administration of nitroglycerin. METHODS: This randomized, double-blind clinical and descriptive pharmacokinetic study was carried out at the gynecology departments at Virchow Hospital and Charité Hospital (both university hospitals of Humboldt University, Berlin, Germany) between June 1994 and July 1996 in patients scheduled for elective cesarean delivery under general anesthesia. At the time of the uterine puncture incision, either 0.25 mg or 0.5 mg of nitroglycerin or a physiologic saline solution was administered as an intravenous bolus. Intraoperatively, maternal and neonatal pulse rates and blood pressure were monitored closely. The surgeons estimated reduction in uterine tone and the ease of fetal extraction by means of defined scales. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and from umbilical blood. RESULTS: Ninety-seven patients were included in the statistical evaluation of the study; 32 received 0.25 mg of nitroglycerin, 34 received 0.5 mg of nitroglycerin, and 31 received placebo. The evaluation of the surgeons' estimation revealed no significant difference in ease of fetal extraction (statistical power 0.7) and no significant reduction in uterine tone under treatment with both nitroglycerin dosages in comparison with placebo. Only substance-specific maternal side effects were noted. The neonates' conditions were not affected by administration of nitroglycerin. The median fetal-maternal ratio of venous nitroglycerin plasma levels was approximately 1:400 in the 0.25-mg nitroglycerin group and 1:160 in the 0.5-mg nitroglycerin group. Approximately 11-12 times more nitroglycerin was detected in the venous umbilical branch than in the arterial branch. CONCLUSION: Administration of nitroglycerin leads to no clinically relevant easing of fetal extraction, at least not in elective cesarean deliveries after the 34th week of gestation. With regard to pharmacokinetics, the measured median fetal-maternal venous nitroglycerin concentration was 1:400 in the 0.25-mg group and 1:160 in the 0.5-mg group.

Adult↗

Operative results after primary and secondary debulking-operations in advanced ovarian cancer (AOC).

OBJECTIVE: To assess the role of primary and secondary radical surgery in advanced ovarian cancer (AOC). DESIGN: Retrospective study. METHODS: One hundred and fifty-one patients with AOC (FIGO III/IV) underwent altogether 191 extended multivisceral operations between 1/1992 and 2/1998. The statistic analysis compared the primary with the secondary operations. RESULTS: One hundred and seventeen patients had a primary, 63 patients had a secondary and 18 patients a tertiary operation because of relapse of ovarian cancer. Surgical procedures entailed respectively: small-bowel-resection (21%/48%), colon resection (39%/58%), colostomy (9%/11%), ileostomy (2%/4%), ileum-pouch (0%/6), splenectomy (3%/3%), pelvic floor-covering (4%/6%), peritoneal removal (24%/21%), infrared contact coagulation (4%/6%). Seventy-five percent of the patients had no complications: relaparotomy (3%/3%), fistula (3%/6%), short-bowel-syndrome (5%/11%), postoperatively mortality (2%/6%). Postoperative tumor-free were 26%/22%, 57% and 65% had residual disease < or = 2 cm, 16%/13% > 2 cm. CONCLUSIONS: Radical multivisceral surgery is feasible, safe and efficient in primary as well in secondary situation of advanced ovarian cancer.

Adult↗

[Optimal use of MRI mammography from the economic viewpoint].

With the introduction of the contrast agent gadolinum DTPA there were hopes that "MRM" would prove to be the investigatory technique that would largely solve the problems of breast diagnostics. However, after the early years of acceptance, the new method of investigation became a subject of controversy. Nonetheless, MRM today occupies a recognized place in diagnostics for certain indications. It is still true, however, that reliable use of this procedure requires a great deal of experience, since there is a relatively large area of overlap between benign and malignant tumors. Further, the costs are significantly higher than those for conventional methods of investigation. New studies that have been conducted at the Charité, Campus Virchow Medical Center in Berlin, suggest that, if one takes the relevant indications into account, MRM can be economic and contribute significantly to cost reduction. Application of a newly developed software package has shown that the good discrimination in a suspect area resulting from contrast agent enhancement makes possible a reliable differentiation between malignant and benign tissue changes. A further result was that, when certain boundary conditions are satisfied, a contrast agent bolus of 0.1 mmol/kg BW is sufficient, making a double dose (0.2 mmol/kg BW) unnecessary.

Breast Neoplasms↗

[Tocolysis with a nitroglycerin patch].

We would like to present a 22 year old nullipara where preterm labor was successfully tocolysed using a nitro-glycerine path without sequellae side effects. Potential advantages and disadvantages of a transdermal nitro-glycerine delivery system in comparison to the commonly used intravenous fenoterol tocolysis is discussed.

Administration, Cutaneous↗

[Cervix carcinoma: staging, therapy, after-care. Experiences with magnetic resonance tomography of cervix carcinoma based on recent literature 1993 to 1997].

The investigation of cervix carcinoma with magnetic resonance tomography (MRT) is still controversially discussed with regard to its diagnostic value as well as for planning radiation therapy. The purpose of this article is to present and discuss papers published between 1993 and 1997 in this field with respect to the technique used, the contrast media applied and its clinical value. A literature search using three different databases (Medline, Embase, Cancerlit) identified 39 publications, which were then analysed. Despite the partially suboptimal presentation of results in these papers MRT proved superior to other imaging modalities. Due to better demarcation of cervix carcinoma with MRT, it was possible to calculate tumor value as well as to correctly judge the infiltrative character. This allows for a more precise treatment and staging of the patient's prognosis. In the future, MRT might be useful in diagnosing recurrence at relatively early stage. Unfortunately lymphatic nodes can only be insufficiently verified using MRT.

Cervix Uteri↗

Transvaginal color Doppler sonography and conventional sonography in the preoperative assessment of adnexal masses.

OBJECTIVE: This investigation was undertaken to evaluate the predictive value of the blood flow velocity as measured by transvaginal color Doppler sonography (CDS) and conventional sonographic criteria in the preoperative assessment of ovarian tumors. METHODS: 98 patients who were admitted for surgery with a suspicion of an adnexal mass (69 benign tumors, 4 borderline tumors, and 25 malignant tumors) were prospectively studied with transvaginal sonography (TVS) and CDS. Pulsatility index of blood flow velocity waveforms was evaluated by CDS and compared with established sonographic criteria for discriminating between benign and malignant ovarian tumors. RESULTS: TVS had a sensitivity of 91% and a specificity of 84% in detecting malignant ovarian tumors compared with CDS with a sensitivity of 90% and a specificity of 74%, using 1.1 as a cut-off value for the pulsatility index. The specificity of CDS was higher in postmenopausal (88%) than in premenopausal (63%) patients. Using TVS and CDS combined, the sensitivity and specificity of diagnosing malignant ovarian tumors could be increased to 95% and 86%. CONCLUSION: In premenopausal patients, TVS is clearly a more sensitive and more specific technique than CDS in correctly identifying benign and malignant ovarian tumors, whereas in postmenopausal patients, CDS gives useful additional information concerning blood vessel resistance. If CDS is used as an additional technique to TVS, it can increase the sensitivity and specificity of TVS in discriminating between benign and malignant ovarian tumors.

Adnexal Diseases↗

Immunostaining of p53 protein in ovarian carcinoma: correlation with histopathological data and clinical outcome.

OBJECTIVE: The objective of this study was to analyze the incidence of immunohistochemically detectable p53 protein accumulation in epithelial ovarian carcinomas and to correlate these data with the clinical outcome so as to clarify further the role of p53 mutations in prognosis with these patients. METHODS: Tumor tissues from 179 patients with epithelial ovarian carcinoma were used for immuno-histochemical analysis with monoclonal antibody DO1 and BP 53-12-1 on formalin-fixed, paraffin-embedded tissue. RESULTS: A total of 78 cases (44%) showed positive nuclear p53 staining. The p53-positive cases were found in all histological types of epithelial ovarian tumors. p53 staining was found in tumors of all stages with a higher percentage of positive cases in stage IV ovarian carcinomas (not significant). Poorly differentiated carcinomas showed a significantly higher percentage of p53 protein expression than did highly differentiated tumors (P = 0.0002). Clinical follow-up of up to 14 years (median 25 months) showed a slightly but not significantly shortened disease-free and overall survival time for patients with p53-positive epithelial ovarian carcinomas. CONCLUSIONS: We conclude from our data that p53 expression in ovarian carcinoma is associated with poor differentiation but not with the disease being in an advanced stage. There was a tendency for shortened disease-free and overall survival for patients with p53-positive tumors.

Adult↗

[Three-dimensional ultrasound study (3-D sonography) of the female breast].

Three-dimensional sonography of the mamma with a Voluson annular array transducer (10 MHz) (Kretztechnik, Austria) is a new method applicable in differential diagnosis of mamma foci. 50 patients (19 of them with breast cancer) were thus pre-surgically examined. Both sectional and stereoscopic representations were made use of. The suspected diagnoses and their correspondences with post-surgical findings were compared to the correspondences obtained through 2D-sonography. 3D-sonography produced 4 cases of the incorrectly positive diagnosis breast cancer, 2D-sonography 2 cases of incorrectly negative diagnoses. Other advantages of 3D-sonography over 2D-sonography include: better judgement of the conditional of focal environs (infiltration), existence and form of intracystic structures and of multifocal disease, short duration of examination, possible re-diagnosing of stored data.

Breast↗

[Significance of PCNA proliferating fraction for prognosis of ovarian carcinoma].

The prognostic value of the PCNA-proliferative fraction as compared to conventional clinical and histomorphological factors (FIGO-stage, tumour type, histological grading, lymph node status, size of residual tumour) was investigated in 81 ovarian cancer patients. Categorisation of PCNA-expression into tumours with low and high proliferative activity (< 20%/ > or = 20% according to laboratory standards) had the highest prognostic value. Categorisation on the basis of the median value (< or = 34%/> 34%) or classification of PCNA as a continuous variable did not prove advantageous. PCNA-proliferative fraction was significantly directly correlated with histological grading (p = 0.006). Tumours with a high PCNA expression had a greater frequency of macroscopically detectable residual tumours. In univariate survival analyses patients with highly proliferating tumours had a worse outcome than patients with tumour of low proliferation (PCNA </> or = 20%/20%, p = 0.012; PCNA < or = 34%/ > 34%, p = 0.08). The result was consistent in subgroup of FIGO III-tumours (p = 0.031, PCNA < 20%/> or = 20%), of FIGO l-tumours (p = 0.036, PCNA < 20%/> or = 20%), of carcinomas without post-operative residual tumour (p = 0.03 PCNA < 20%/> or = 20%) and also of FIGO III-tumour without residual tumours (p = 0.041 PCNA < 20%/> or = 20%). Multivariate survival analysis comprising all the patients revealed PCNA expression (< 20%/> or = 20%) as an independent prognostic factor second to the size of the residual tumour. In patients with FIGO III-tumours PCNA proves significant as an independent factor after the size of the residual tumour was removed from the model. Thus, PCNA provides additional information which may prove beneficial in determining prognostic estimates for ovarian cancer.

Adult↗

Internal jugular vein thrombosis caused by resistance to activated protein C as a complication of ovarian hyperstimulation after in-vitro fertilization.

We present a case of a 24 year old woman who became pregnant (twins) after human menopausal gonadotrophin (HMG)-induced ovarian stimulation, in-vitro fertilization (IVF) and subsequent embryo transfer. She developed a right internal jugular vein thrombosis as a complication of severe ovarian hyperstimulation syndrome (OHSS) 28 days after embryo transfer. The thrombosis developed in spite of anticoagulation with low-dose heparin. Later a resistance to activated protein C (APC) or Dahlbäck disease was diagnosed. Due to a new test procedure (accelerin inactivation test), the diagnosis was possible even under anticoagulation treatment. The coincidence of hyperstimulation and internal jugular vein thrombosis with the concurrent diagnosis of resistance to APC has not been published previously. The benefit of general screening for resistance to APC before admission to the IVF programme should be weighed. Targeted selection of a group of high-risk women would therefore be made possible.

Adult↗